Medical article having a hydrophilic coating

ABSTRACT

A process for coating a polymer surface with a hydrophilic coating with low friction in wet condition. The process comprises applying to the polymer surface a solution containing between 0.05 to 40% of a compound which comprises at least two unreacted isocyanate groups per molecule, evaporating the solvent, applying a solution containing between 0.5 to 50% of polyethylene oxide to the thus treated polymer surface and then evaporating the solvent of the last mentioned solution, and curing the coating at elevated temperature. The process is preferably carried out in the presence of a catalyst for the curing of isocyanate.

This application is a division of application Ser. No. 487,102, filed onApr. 21, 1983 now U.S. Pat. No. 4,459,317.

The present invention relates to a process for coating a polymer surfacewith a hydrophilic coating which has a low coefficient of friction whenwetted with a water based liquid, as well as medical articles beingcoated with a hydrophilic coating according to said process.

PRIOR ART

British patent No. 1 600 963 (Biosearch Medical Products Inc.) disclosesa process for applying a hydrophilic coating which coating consists ofan interpolymer of polyvinylpyrollidone and polyurethane, said coatinghaving a much lower coefficient of friction in wet condition than in drycondition. Such coatings are, among other things, especially useful formedical instruments intended to be entered in body cavities, because theinstrument gives a good hand grip in dry condition while simultaneouslybecoming very slippery when it gets in contact with body liquids or wetmucuous membranes, and thus can be inserted easily without damage to thepatient. The process disclosed in said British patent has been shown tobe useful for accomplishing such coatings, but is on the other hand toocomplicated for being suitable for large-scale production. The processdescribed in Example 1 in the patent thus comprises not less than tensteps, whereby one of the steps takes 6 hours to carry through. Afurther disadvantage with this known process is that cracks are oftenformed in the coating.

DISCLOSURE OF THE INVENTION

The object of the invention is to provide a process for the preparationof a hydrophilic coating that has a much lower coefficient of frictionin wet condition and which process is more simple and more rapid tocarry out than the process disclosed in the above-mentioned Britishpatent No. 1 600 963. Further the process also gives a coating that isfree from cracks. These objects of the invention have surprisingly beenachieved by applying a solution containing between 0.05-40%(weight/volume, that is kg/liter) of a compound containing at least twounreacted isocyanate groups per molecule to a polymer surface,evaporating the solvent, applying a solution of polyethylene oxidecontaining between 0.5% to 50% (weight/volume) to the thus treatedpolymer surface and then evaporating the solvent of the last mentionedsolution, and curing the coating at elevated temperature.

The invention is explained in detail in the following.

The process according to the invention can be used for coating manydifferent types of polymer surfaces, such as latex rubber, otherrubbers, polyvinylchloride, other vinyl polymers, polyurethanes,polyesters and polyacrylates. The process has been found to beespecially useful for latex, polyvinylchloride and polyurethanes.

The process according to the invention comprises applying to a polymersurface a compound containing at least two unreacted isocyanate groupsper molecule dissolved in a solvent, by dipping, spraying or the likeand then evaporating the solvent preferably by air drying. This stepforms a coating with unreacted isocyanate groups on the polymer surface.Examples of isocyanate containing compounds that may be used arepolyisocyanates such as polymethylene polyphenyl isocyanate,4,4'-diphenylmethane diisocyanate, and 2,4-toluene diisocyanate.Prepolymers or other addition products of isocyanates and polyols areespecially useful, for example prepolymers between toluene diisocyanate,or hexamethylene diisocyanate, and trimethylolpropane, or trimerizedhexamethylene diisocyanate biuret. Such prepolymers are commerciallyavailable under the trade name Desmodur (Bayer AG).

The solvent for the isocyanate compound is preferably one that does notreact with isocyanate. The preferred solvent is methylene chloride butit is also possible to use ethylacetate, acetone, chloroform, methylethyl ketone and ethylene dichloride, for example.

The isocyanate solution may advantageously contain between 0.5% to 10%(weight/volume) of isocyanate compound, and may preferably containbetween 1% to 6% (weight/volume) of isocyanate compound. Generally, thesolution need to be in contact with the surface only briefly, forexample 5 to 60 seconds. In the case of coating of for example rubberlatex it is desirable with a longer period, for example 1 to 100minutes, to obtain a strong adherence. Another method to increase theadherence is to swell the polymer surface beforehand in a suitablesolvent. A still further method is to choose a solvent for theisocyanate, such that the solvent in itself has the ability to swell ordissolve the polymer surface which is to be coated.

Following the evaporation of the solvent for the isocyanate from thepolymer surface, the surface is coated with polyethylene oxide dissolvedin a solvent, whereby a hydrophilic surface is obtained which subsequentto final curing of the isocyanate normally consists of a polyethyleneoxide-polyurea interpolymer. The polyethylene oxide used should have amean molecular weight of between 10⁴ to 10⁷, and the preferred meanmolecular weight is about 10⁵. Polyethylene oxide having such amolecular weight is commercially available, for example under the tradename POLYOX® (Union Carbide Corporation, U.S.A.). Examples of suitablesolvents for polyethylene oxide that can be used are methylene chloride(preferred), ethyl acetate, acetone, chloroform, methyl ethyl ketone andethylene dichloride. The proportion of polyethylene oxide in thesolution is preferably between 0.5% to 10% (weight/volume) and mostpreferred between 2 to 8% (weight/volume). The polyethylene oxide in thesolvent is applied by dipping, spraying or the like for a short periodof time, for example during 5 to 50 seconds. After the polyethyleneoxide solution has been applied to the coated surface, the solvent isevaporated preferably by air drying. The residual traces of solvent areremoved at the curing of the coating which is preferably performed at atemperature of 50° to 100° C., in for example an oven, and during 5 to30 minutes. All the other steps in the process may be performed atambient temperature.

The purpose of the curing, which is advantageously conducted in thepresence of a water-containing gas such as ambient air, is to bind theisocyanate compounds together to the formation of a stable non-reactivenetwork that binds the hydrophilic polyethylene oxide. The isocyanategroups reacts with water at the curing and yields an amine which rapidlyreacts with other isocyanate groups to the formation of a ureacross-link.

According to the invention it has surprisingly been found possible tosimultaneously reduce the low friction of the hydrophilic surface, toimprove the adherence of the coating, and to shorten the necessaryreaction times and curing times, by using some additives to the solutionof isocyanate and/or the solution of polyethylene oxide. Such a suitableadditive comprises different known catalysts for isocyanate curing.These catalysts may be dissolved in either the isocyanate solution orthe polyethylene oxide solution but are preferably dissolved in thelatter. Different types of amines are especially useful, for exampledifferent diamines, but also for example triethylene diamine.Preferably, an aliphatic amine is employed which is volatilizable at thedrying and curing temperatures used for the coating, and whichfurthermore is non-toxic. Examples of suitable amines areN,N'-diethylethylendiamine, hexamethylendiamine, ethylendiamine,paradiaminobenzene, 1,3-propandiol-para-aminobenzoic acid diesther,diaminobicyclo octane, and triethanolamine. The proportion of catalystin the polyethylene oxide solution is suitably between 0.1 to 50% byweight of the amount of polyethylene oxide, preferably between 0.1 to10% by weight. Some of the above-mentioned amines, particularly thediamines, can also react with isocyanate and thereby contribute to thecross-linking of the isocyanate compounds that give the desired strongadherence between the hydrophilic coating and the polymer surface.

Furthermore, it has surprisingly been shown to be possible to reduce thelow friction for the hydrophilic surface still further, by way ofdissolving a polymer in the isocyanate solution. Examples of suitablepolymers are polyesters, polyvinyl compounds such as polyvinylchlorideor polyvinylacetate, polyurethanes, polyisocyanates, or copolymers ofthese. These otherwise substantially inert polymers are supposed to givethe surprisingly reduced friction at the surface mainly because theyobstruct an undesired diffusion of not yet cross-linked isocyanatecompounds out into the polyethylene oxide layer. A further reason forthe low friction may be that the addition of a polymer enhance theelasticity of the coating. The proportion of dissolved polymer in theisocyanate solution is suitably between 0.5 to 20% by weight of thesolution, preferably between 2 to 10% by weight.

The obtained hydrophilic coating evidently contains an appreciableamount of partly freely movable polyethylene oxide chains. Thus it hasbeen shown that the coating can complex-bind a substantial amount ofelemental iodine (compare Example 5), as is also the case with freepolyethylene oxide. Such a iodine containing hydrophilic andantibacterial coating is advantageous for many medical uses, for examplefor urinary catheters which are intended for insertion in the urethrafor extended periods of time and which otherwise is a common cause ofinfections. The iodine containing coating is suitably prepared by finaldipping in a KI/I₂ -solution containing at least 1% by weight of iodine,followed by drying, possibly preceeded by rinsing in a solvent.

The invention is illustrated in detail in the following Examples.

EXAMPLE 1

A pentamer of toluene diisocyanate of cyanurate type (named Desmodur IL;Bayer AG) was dissolved in methylene chloride to a concentration of 2%(weight/volume). The solution also contained a minor amount of butylacetate. A urinary PVC catheter was dipped in this solution during 30seconds. The catheter was allowed to dry at ambient temperature during30 seconds, whereupon it was dipped in a solution of 6% (weight/volume)polyethylene oxide (type WSRN10; Union Carbide) in methylene chlorideduring 5 seconds. The catheter was then allowed to dry at ambienttemperature during 60 seconds, and then during 20 minutes at 70° C.above a bowl filled with water. The catheter was finally allowed to coolto ambient temperature during 20 minutes whereupon it was rinsed inwater. The catheter had a slippery and adhering surface.

EXAMPLE 2

A solution containing 0.5% (weight/volume) of the isocyanate Desmodur IL(compare Example 1) and 5% (weight/volume) of a copolymer of PVC andpolyvinylacetate (20% vinylacetate/80% PVC) named LONZA CL 4520 inmethylene chloride was prepared. A PVC-catheter was dipped in thissolution during 15 seconds and was then dried at ambient temperatureduring 30 seconds, whereupon it was dipped in a solution containing 6%(weight/volume) polyethylene oxide (type WSRN10; Union Carbide;approximate mean molecular weight 100.000) and 0.23% (weight/volume)triethylendiamine in methylene chloride. The catheter was dried during60 seconds at ambient temperature and then during 20 minutes at 70° C.above a bowl filled with water. It was then allowed to cool and wasfinally rinsed in water. The catheter had a slippery and adheringsurface.

EXAMPLE 3

A latex catheter was swelled in methylene chloride during 30 minutes.The catheter was then dried at ambient temperature during 60 seconds,and was then dipped during 30 seconds in a solution containing 6%(weight/volume) of Desmodur L2291 (a trimerized hexamethylenediisocyanate of biuret type obtainable from Bayer AG) in methylenechloride. The catheter was dried at ambient temperature during 60seconds and was then dipped in a solution containing 6% (weight/volume)polyethylene oxide (type WSRN10, Union Carbide) in methylene chloride.The catheter was then dried during 60 seconds at ambient temperature andfinally during 20 minutes at 70° C. above a bowl filled with water.

EXAMPLE 4

The inner of a two meter long hose of PVC (inner diameter 3 mm; outerdiameter 4.5 mm) was flushed with different solutions and drying agentsin the following orders and periods of time:

5% (weight/volume) of Desmodur IL (compare Example 1) dissolved inmethylene chloride and during 30 seconds; gaseous nitrogene of ambienttemperature during 30 seconds; 2.5% (weight/volume) of polyethyleneoxide (type WSRN10, Union Carbide) dissolved in methylene chloride andduring 10 seconds; gaseous nitrogene of ambient temperature during 60seconds.

The hose was then placed in an oven and gaseous nitrogene was flushedthrough the hose during 20 minutes. The temperature of the oven was 70°C. The nitrogene used was first bubbled through water. Finally the hosewas taken out from the oven and water was flushed through the hoseduring 1hour. The inside of the thus treated hose had a hydrophiliccoating,

EXAMPLE 5

A urinary catheter of latex rubber was dipped during 30 seconds in asolution containing 5% (weight/volume) of Desmodur IL (compareExample 1) in methylene chloride. The catheter was then dried at ambienttemperature during 60 seconds and was then dipped in a solutioncontaining 5% (weight/volume) polyethylene oxide (type WSRN10) inmethylene chloride. The catheter was dried during 60 seconds at ambienttemperature and was then cured during 20 minutes at 70° C. above a bowlof water.

After cooling the catheter it was rinsed in water and was then dipped ina saturated water solution of potassium iodide being saturated withelemental iodine. Finally the catheter was rinsed in a stream of waterand was allowed to dry in ambient air. The catheter had a brown colourand chemical analysis showed that it contained iodine.

I claim:
 1. A medical article for insertion in the body which isprovided with a hydrophilic coating by applying to the article asolution containing between 0.05 to 40% (weight to volume) of a compoundwhich comprises at least two unreacted isocyanate groups per molecule,evaporating the solvent, applying a second solution containing between0.5 to 50 % (weight to volume) of polyethylene oxide having a meanmolecular weight of between 10⁴ to 10⁻⁷ to the thus treated article andthen evaporating the solvent of the second solution, and curing thecoating at elevated temperature.
 2. A medical article according to claim1 wherein the solution of polyethylene oxide or the solution ofisocyanate contains a catalyst that accelerates the curing of theisocyanate.
 3. A medical article according to claim 2 wherein thecatalyst comprises an amine.
 4. A medical article according to claim 2wherein the catalyst comprises a diamine or triethylene diamine.
 5. Amedical article according to claims 1, 2 or 3 wherein the isocyanatesolution contains a polymer.
 6. A medical article according to claim 5wherein the polymer in the isocyanate solution is selected from thegroup consisting of polyesters, polyvinyl compounds, polyurethanes,polyisocyanates, or copolymers thereof.
 7. A medical article accordingto claim 1 wherein the curing is performed in the presence of awater-containing gas.
 8. A medical article according to claim 1 whereinthe polymer surface to be coated comprises a polymer selected from thegroup consisting of latex, polyvinylchloride, and polyurethane.
 9. Amedical article according to claim 1 wherein the hydrophilic coating istreated with iodine.
 10. A medical article according to claim 1 whichcomprises a catheter.